Emerging Immunotherapies for Advanced Non-Small-Cell Lung Cancer DOI Creative Commons

Emily Wolf,

Guilherme Sacchi de Camargo Correia,

Shenduo Li

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 128 - 128

Published: Jan. 27, 2025

Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung (NSCLC) is most common type cancer, with nearly half all patients diagnosed at an advanced stage. Immune checkpoint inhibitors (ICIs) harness host immune system to combat malignant cells. ICIs, which target programmed death-ligand 1 (PD-L1), cell death (PD-1), and cytotoxic T-cell lymphocyte-4 (CTLA-4), have transformed treatment landscape for NSCLC. While a subset experiences long-term durable response, will develop disease progression. New drugs targeting novel pathways are being tested in clinical trials improve efficacy immunotherapy overcome resistance patterns. This review aims summarize currently available ICIs NSCLC describe emerging immunotherapies recently published data from phase I/II trials.

Language: Английский

Harnessing lipid metabolism modulation for improved immunotherapy outcomes in lung adenocarcinoma DOI Creative Commons
Yang Chen, Yu Zhou, Ran Ren

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(7), P. e008811 - e008811

Published: July 1, 2024

Background While anti-programmed cell death protein-1 (PD-1) monotherapy has shown effectiveness in treating lung cancer, its response rate is limited to approximately 20%. Recent research suggests that abnormal lipid metabolism patients with adenocarcinoma may hinder the efficacy of anti-PD-1 monotherapy. Methods Here, we delved into patterns The Cancer Genome Atlas (TCGA)-lung (LUAD) and their correlation immune microenvironment’s cellular infiltration characteristics tumor. Furthermore, score (LMS) system was constructed, based on LMS system, further performed screening for potential agents targeting metabolism. mechanism MK1775 validated using RNA sequencing, co-culture technology, vivo experiments. Results We developed an LSM identified a sensitizing agent, MK1775, which targets enhances effects treatment. Our results demonstrate inhibits tumor progression by influencing crosstalk between cells tumor-associated macrophages CD8 + T cells, thereby increasing Further, found inhibited phosphatidylinositol 3-kinase(PI3K)/AKT/mammalian target rapamycin (mTOR) signaling pathway, one hand downregulated FASN-mediated synthesis fatty acids (FAs) inhibit acid oxidation macrophages, other hand, promoted IRF-mediated secretion CXCL10 CXCL11 facilitate cells. Conclusions These findings emphasize important role shaping complex microenvironment. By manipulating intricate intricacies within microenvironment, can uncover develop promising strategies sensitize immunotherapy, potentially revolutionizing cancer treatment approaches.

Language: Английский

Citations

11
Immunotherapy in resectable NSCLC: Answering the question or questioning the answer? DOI
Si‐Yang Liu, Weineng Feng, Yi‐Long Wu

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(5), P. 727 - 731

Published: May 1, 2024

Language: Английский

Citations

10
High CD38 expression defines a mitochondrial function-adapted CD8+ T cell subset with implications for lung cancer immunotherapy DOI Creative Commons

Lei-lei Lv,

Jiawei Zhai,

Jinrui Wu

et al.

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(2)

Published: Jan. 3, 2025

Despite identifying specific CD8+ T cell subsets associated with immunotherapy resistance, the molecular pathways driving this process remain elusive. Given potential role of CD38 in regulating function, we aimed to investigate accumulation CD38+CD8+ cells lung cancer and explore its resistance. Phenotypic analysis tumoral from both patients immunotherapy-resistant preclinical models revealed that CD38-expressing consist CD38hi CD38int subsets. These exhibited higher expression exhaustion markers displayed dysregulated mitochondrial bioenergetics. Notably, increased levels CD38hiCD8+ peripheral, but not central, tumor microenvironment were a favorable response anti-PD-1 therapy non-small-cell correlated depth clinical regression. This was evidenced by greater depletion regional infiltration. In immune checkpoint blockade (ICB)-resistant murine models, PD-L1 mAbs alone failed effectively reduce levels. combination EGCG selectively restricted infiltration enhanced IFN-γ production, significantly improving survival carcinoma model. The restoration sensitivity linked improved function cells, which validated established relationship between production metabolism. Collectively, our data highlight CD38-coupled dysfunction promoting intrinsic resistance ICB therapy, thereby offering rationale for targeting enhance therapeutic efficacy PD-1 cancer.

Language: Английский

Citations

1
Ginseng polysaccharides circumvent acquired resistance to anti-PD-1 immunotherapy in patients with non-small cell lung cancer DOI Creative Commons
Jumin Huang, Ziming Wang, Feng Li

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107611 - 107611

Published: Jan. 18, 2025

Language: Английский

Citations

1
Emerging Immunotherapies for Advanced Non-Small-Cell Lung Cancer DOI Creative Commons

Emily Wolf,

Guilherme Sacchi de Camargo Correia,

Shenduo Li

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 128 - 128

Published: Jan. 27, 2025

Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung (NSCLC) is most common type cancer, with nearly half all patients diagnosed at an advanced stage. Immune checkpoint inhibitors (ICIs) harness host immune system to combat malignant cells. ICIs, which target programmed death-ligand 1 (PD-L1), cell death (PD-1), and cytotoxic T-cell lymphocyte-4 (CTLA-4), have transformed treatment landscape for NSCLC. While a subset experiences long-term durable response, will develop disease progression. New drugs targeting novel pathways are being tested in clinical trials improve efficacy immunotherapy overcome resistance patterns. This review aims summarize currently available ICIs NSCLC describe emerging immunotherapies recently published data from phase I/II trials.

Language: Английский

Citations

1